tbuckley/cabot-search huggingface dataset:
Cholecystectomy-induced secondary bile acids accumulation ameliorates colitis through inhibiting monocyte/macrophage recruitment
Authors: Yun Liu, Jun Xu, Xinhua Ren, Yu Zhang, Ziliang Ke, Jianhua Zhou, Yang Wang, Yifan Zhang, Yulan Liu
Journal: Gut Microbes (2022)

Although post-cholecystectomy (PC) patients usually have gastrointestinal complications and a higher risk of colorectal cancer, previous studies undetected a heightened risk of inflammatory bowel disease. Thus, we tried to investigate cholecystectomy's impact and pathophysiological mechanism on murine colitis models and clarify the association among fecal bile acids (BAs), mucosal bacterial microbiota, and immune cells in the PC patients. One month or three months after cholecystectomy, mice have induced colitis and tested BAs and fecal microbiota analysis. Next, mice were treated with various cholecystectomy-accumulated bile acids in drinking water for three months before inducing colitis. All 14 paired PC patients and healthy subjects were enrolled for BAs and mucosal microbiota analysis. Cholecystectomy ameliorated DSS-induced murine colitis, accelerated mucosal repair, and induced a significant shifting of fecal microbiota and BAs profiles under colitis status, which featured a higher relative abundance of species involved in BAs metabolism and increased secondary BAs concentrations. Cholecystectomy-associated secondary BAs (LCA, DCA, and HDCA) also ameliorated DSS-induced colitis and accelerated mucosal repair in mice. Cholecystectomy and specific secondary BAs treatments inhibited monocytes/macrophages recruitment in colitis mice. In vitro, cholecystectomy-associated secondary BAs also downregulated monocytes chemokines in the THP-1 derived macrophages through activation of the LXRα-linked signaling pathway. The alterations of mucosal microbiota and fecal BAs profiles were found in the PC patients, characterized as increased species with potential immuno-modulating effects and secondary BAs, which were negatively associated with peripheral monocytes levels. Cholecystectomy-induced secondary bile acids accumulation ameliorated colitis through inhibiting monocyte/macrophage recruitment, which might be mediated by the LXRα-related signaling pathway. Cholecystectomy, after 3 months follow-up, has an immune-regulatory role in murine colitis, preliminarily explaining that no increased risk of IBD had been reported in the PC patients, which still warrants further studies.
Somatic copy number alteration and fragmentation analysis in circulating tumor DNA for cancer screening and treatment monitoring in colorectal cancer patients
Authors: Ariane Hallermayr, Tobias Wohlfrom, Verena Steinke-Lange, Anna Benet-Pagès, Florentine Scharf, Ellen Heitzer, Ulrich Mansmann, Christopher Haberl, Maike de Wit, Holger Vogelsang, Markus Rentsch, Elke Holinski-Feder, Julia M. A. Pickl
Journal: Journal of Hematology & Oncology (2022)

Analysis of circulating free DNA (cfDNA) is a promising tool for personalized management of colorectal cancer (CRC) patients. Untargeted cfDNA analysis using whole-genome sequencing (WGS) does not need a priori knowledge of the patient´s mutation profile.Here we established LIquid biopsy Fragmentation, Epigenetic signature and Copy Number Alteration analysis (LIFE-CNA) using WGS with ~ 6× coverage for detection of circulating tumor DNA (ctDNA) in CRC patients as a marker for CRC detection and monitoring.We describe the analytical validity and a clinical proof-of-concept of LIFE-CNA using a total of 259 plasma samples collected from 50 patients with stage I-IV CRC and 61 healthy controls. To reliably distinguish CRC patients from healthy controls, we determined cutoffs for the detection of ctDNA based on global and regional cfDNA fragmentation patterns, transcriptionally active chromatin sites, and somatic copy number alterations. We further combined global and regional fragmentation pattern into a machine learning (ML) classifier to accurately predict ctDNA for cancer detection. By following individual patients throughout their course of disease, we show that LIFE-CNA enables the reliable prediction of response or resistance to treatment up to 3.5 months before commonly used CEA.In summary, we developed and validated a sensitive and cost-effective method for untargeted ctDNA detection at diagnosis as well as for treatment monitoring of all CRC patients based on genetic as well as non-genetic tumor-specific cfDNA features. Thus, once sensitivity and specificity have been externally validated, LIFE-CNA has the potential to be implemented into clinical practice. To the best of our knowledge, this is the first study to consider multiple genetic and non-genetic cfDNA features in combination with ML classifiers and to evaluate their potential in both cancer detection and treatment monitoring. Trial registration DRKS00012890.
Mortality in patients with end‐stage liver disease above model for end‐stage liver disease 3.0 of 40
Authors: W. Ray Kim, Ajitha Mannalithara, Paul Y. Kwo, C. Andrew Bonham, Allison Kwong
Journal: Hepatology (2022)

Since the implementation of the model for end-stage liver disease (MELD) score to determine waitlist priority for liver transplant (LT) in 2002, the score has been capped at 40. Recently, the MELD 3.0 score was proposed to improve upon MELD-Na. Here, we examine waitlist mortality and LT outcomes in patients with MELD 3.0 ≥ 40 to assess the potential impact of uncapping the score.
Joint Study of Extracranial Arterial Occlusion
Authors: José B. Gomensoro
Journal: JAMA (1973)

One hundred seventy-seven patients with transient ischemic attacks and a radiographic diagnosis of stenosis or occlusion at the cervical carotid artery bifurcation were included in our study. They were categorized by symptoms and type and extent of plaque. There were more smooth lesions reported in patients with less than 50% stenosis and more rough plaques in those with greater narrowing. Involvement of the cervical bifurcation by atherosclerosis presented a variable radiologic pattern. Seventy patients had unilateral stenosis; 83, bilateral stenosis; and 24, occlusion with contralateral stenosis. Smooth atheromata were described in 59 patients, rough in 87, and mixed lesions in 31. There was good correlation of the interpretation by the surgeon and the neuroradiologist when lesions were far-advanced or were roughened, and poor correlation when the lesions were minimal or smooth.
Health Care Quality
Authors: Paul D. Cleary
Journal: JAMA (1997)

The goal of this article is to address, from the perspective of users of the health care system (consumers), the following questions: What are the most important health care quality gaps and/or challenges; what major changes should we anticipate in this area in the near future; and what should be the role of federal and state agencies, accreditation organizations, and philanthropic foundations in addressing these challenges? We discuss the needs, challenges, and potential action steps for increasing the prominence of the user's perspective in 3 areas: (1) the conceptualization and definition of quality; (2) the measurement of quality; and (3) routine quality assessment and improvement. The article concludes by making recommendations about the role that different agencies and organizations can and should play in meeting these challenges.
Asbestos and Smoking
Authors: Irving J. Selikoff
Journal: JAMA (1979)

More than ten years ago,The Journalpublished information that some cancer deaths associated with prior asbestos exposure might be related to more than asbestos alone and could be multifactorial in origin.<sup>1</sup>It had been found that inhalation of the mineral fibers greatly increased the already high lung cancer risk for cigarette smokers. In the group studied, it was calculated that asbestos workers who smoked cigarettes had roughly 90 times the risk for similar men who neither smoked nor worked with asbestos. In the decade since, this has been amply confirmed,<sup>2</sup>and the observations made provide much clinical guidance in the care and surveillance of those who have been exposed in the past and who are now in the future at risk of asbestos-associated disease. The two most common asbestos-induced cancers are lung cancer and mesothelioma. The former is usually related to cigarette smoking; the latter is not.
A Randomized Trial to Increase Smoking Intervention by Physicians
Authors: Thomas E. Kottke
Journal: JAMA (1989)

Sixty-six physicians were randomized to three groups to conduct a 1-month campaign to help their patients stop smoking. The workshop group received free patient education materials and a 6-hour training workshop. The materials group received free patient education materials, and the no-assistance group received nothing. A telephone interview was completed with 89% of the 6767 eligible adult patients seen during the month of the campaign. The brief training program and patient education materials marginally increased the smoking intervention activities of volunteer physicians in private practice. Both workshop and materials physicians asked 54% of their smoking patients to stop; no-assistance physicians asked 40%. One year later, 36% of patients who had not even been asked by their doctors if they smoked reported that they had tried to stop smoking. If the physician had asked the patient if he or she smoked, the probability of a quit attempt was 47%. Patients who had been asked if they smoked were more likely to claim to have stopped (13%) than patients who had not been asked (9%). However, the proportion of patients claiming continued abstinence (range, 12% to 14%) was not related to the group of the physician. (<i>JAMA</i>. 1989;261:2101-2106)
The Quality of Mercy
Authors: Daniel P. Sulmasy
Journal: JAMA (1992)

<h3>Objective.</h3> —To assess (1) the effect of an ethics education intervention for medical house officers on practices surrounding "Do Not Resuscitate" (DNR) orders and (2) the association of DNR care with patient diagnosis and demographic variables. <h3>Design.</h3> —A 1-year randomized, controlled trial. <h3>Setting.</h3> —An urban, university teaching hospital. <h3>Participants.</h3> —Eighty-eight internal medicine house officers. <h3>Intervention.</h3> —House officers were arbitrarily assigned to four "firms." One firm was randomized to an extensive ethics education intervention (EI), one to a limited intervention, and two served as controls. <h3>Main Outcome Measures.</h3> —Charts of patients with DNR orders were reviewed for compliance with the hospital's DNR policy, which instructs that when DNR orders are written there should be (1) an attending signature, (2) documentation of reasons, (3) appropriate consent, and (4) attention to 11 concurrent care concerns (CCCs) (eg, the appropriateness of intubation, tube feedings, hospice). <h3>Results.</h3> —Thirty-nine charts were reviewed before the intervention and 57 after. The number of CCCs per DNR order fell among patients cared for by controls (1.9 to 1.0,<i>P</i>&lt;.05) and rose among patients cared for by the El group (0.9 to 3.8,<i>P</i>&lt;.05). Compliance with the DNR policy varied among patients with differing diagnoses. "Do Not Resuscitate" orders were signed less frequently (<i>P</i>=.01) for patients with the acquired immunodeficiency syndrome (AIDS) (65%) compared with patients who had other diagnoses (85%) or malignancy (91%). Similarly, appropriate consent was recorded for 59% of patients with AIDS, 83% of others, and 85% of those with malignancy (<i>P</i>&lt;.05). The number of CCCs per DNR was 0.7 for AIDS, 1.4 for others, and 2.4 for malignancy (<i>P</i>&lt;.05). In multivariate regression analysis, house officer ethics education and patient diagnosis, but not patient gender, age, race, or insurance status, were predictors of the number of CCCs per DNR. <h3>Conclusions.</h3> —(1) An extensive ethics education intervention can improve care for DNR patients, especially with respect to CCCs. (2) In this setting, quality of care for DNR patients varied systematically with diagnosis. These results have implications for the design and implementation of ethics education programs. (<i>JAMA</i>. 1992;267:682-686)
Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis
Authors: Xinfang Xie, Emily Atkins, Jicheng Lv, Alexander Bennett, Bruce Neal, Toshiharu Ninomiya, Mark Woodward, Stephen MacMahon, Fiona Turnbull, Graham S Hillis, John Chalmers, Jonathan Mant, Abdul Salam, Kazem Rahimi, Vlado Perkovic, Anthony Rodgers
Journal: The Lancet (2015)
Sphingosine kinase 1 promotes tumor immune evasion by regulating the MTA3-PD-L1 axis
Authors: Poyee Lau, Guanxiong Zhang, Shuang Zhao, Long Liang, Hailun Zhang, Guowei Zhou, Mien-Chie Hung, Xiang Chen, Hong Liu
Journal: Cellular and Molecular Immunology (2022)

Abstract Immune checkpoint blockade (ICB) exhibits considerable benefits in malignancies, but its overall response rate is limited. Previous studies have shown that sphingosine kinases (SPHKs) are critical in the tumor microenvironment (TME), but their role in immunotherapy is unclear. We performed integrative analyses including bioinformatics analysis, functional study, and clinical validation to investigate the role of SPHK1 in tumor immunity. Functionally, we demonstrated that the inhibition of SPHK1 significantly suppressed tumor growth by promoting antitumor immunity in immunocompetent melanoma mouse models and tumor T-cell cocultures. A mechanistic analysis revealed that MTA3 functions as the downstream target of SPHK1 in transcriptionally regulating tumor PD-L1. Preclinically, we found that anti-PD-1 monoclonal antibody (mAb) treatment significantly rescued tumor SPHK1 overexpression or tumor MTA3 overexpression-mediated immune evasion. Significantly, we identified SPHK1 and MTA3 as biological markers for predicting the efficacy of anti-PD-1 mAb therapy in melanoma patients. Our findings revealed a novel role for SPHK1 in tumor evasion mediated by regulating the MTA3-PD-L1 axis, identified SPHK1 and MTA3 as predictors for assessing the efficacy of PD-1 mAb treatment, and provided a therapeutic possibility for the treatment of melanoma patients.
Independent Risk Factors for Atrial Fibrillation in a Population-Based Cohort
Authors: Emelia J. Benjamin
Journal: JAMA (1994)

<h3>Objective.</h3> —To determine the independent risk factors for atrial fibrillation. <h3>Design.</h3> —Cohort study. <h3>Setting.</h3> —The Framingham Heart Study. <h3>Subjects.</h3> —A total of 2090 men and 2641 women members of the original cohort, free of a history of atrial fibrillation, between the ages of 55 and 94 years. <h3>Main Outcome Measures.</h3> —Sex-specific multiple logistic regression models to identify independent risk factors for atrial fibrillation, including age, smoking, diabetes, electrocardiographic left ventricular hypertrophy, hypertension, myocardial infarction, congestive heart failure, and valve disease. <h3>Results.</h3> —During up to 38 years of follow-up, 264 men and 298 women developed atrial fibrillation. After adjusting for age and other risk factors for atrial fibrillation, men had a 1.5 times greater risk of developing atrial fibrillation than women. In the full multivariable model, the odds ratio (OR) of atrial fibrillation for each decade of advancing age was 2.1 for men and 2.2 for women (<i>P</i>&lt;.0001). In addition, after multivariable adjustment, diabetes (OR, 1.4 for men and 1.6 for women), hypertension (OR, 1.5 for men and 1.4 for women), congestive heart failure (OR, 4.5 for men and 5.9 for women), and valve disease (OR, 1.8 for men and 3.4 for women) were significantly associated with risk for atrial fibrillation in both sexes. Myocardial infarction (OR, 1.4) was significantly associated with the development of atrial fibrillation in men. Women were significantly more likely than men to have valvular heart disease as a risk factor for atrial fibrillation. The multivariable models were largely unchanged after eliminating subjects with valvular heart disease. <h3>Conclusion.</h3> —In addition to intrinsic cardiac causes such as valve disease and congestive heart failure, risk factors for cardiovascular disease also predispose to atrial fibrillation. Modification of risk factors for cardiovascular disease may have the added benefit of diminishing the incidence of atrial fibrillation. (<i>JAMA</i>. 1994;271:840-844)
Monkeypox DNA levels correlate with virus infectivity in clinical samples, Israel, 2022
Authors: Nir Paran, Yfat Yahalom-Ronen, Ohad Shifman, Shirley Lazar, Ronen Ben-Ami, Michal Yakubovsky, Itzchak Levy, Anat Wieder-Feinsod, Sharon Amit, Michal Katzir, Noga Carmi-Oren, Ariela Levcovich, Mirit Hershman-Sarafov, Alona Paz, Rebecca Thomas, Hadas Tamir, Lilach Cherry-Mimran, Noam Erez, Sharon Melamed, Moria Barlev-Gross, Shay Karmi, Boaz Politi, Hagit Achdout, Shay Weiss, Haim Levy, Ofir Schuster, Adi Beth-Din, Tomer Israely
Journal: Eurosurveillance (2022)

The current monkeypox virus global spread and lack of data regarding clinical specimens’ infectivity call for examining virus infectivity, and whether this correlates with results from PCR, the available diagnostic tool. We show strong correlation between viral DNA amount in clinical specimens and virus infectivity toward BSC-1 cell line. Moreover, we define a PCR threshold value (Cq ≥ 35, ≤ 4,300 DNA copies/mL), corresponding to negative viral cultures, which may assist risk-assessment and decision-making regarding protective-measures and guidelines for patients with monkeypox.
World Field Epidemiology Day 2022: Empowering field epidemiologists to strengthen health systems’ preparedness and response to public health threats
Authors: Carmen Varela Santos, Adam Roth
Journal: Eurosurveillance (2022)

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Age-specific associations between underlying health conditions and hospitalisation, death and in-hospital death among confirmed COVID-19 cases: a multi-country study based on surveillance data, June to December 2020
Authors: Tjede Funk, Francesco Innocenti, Joana Gomes Dias, Lina Nerlander, Tanya Melillo, Charmaine Gauci, Jackie M Melillo, Patrik Lenz, Helena Sebestova, Pavel Slezak, Iva Vlckova, Jacob Dag Berild, Camilla Mauroy, Elina Seppälä, Ragnhild Tønnessen, Anne Vergison, Joël Mossong, Silvana Masi, Laetitia Huiart, Gillian Cullen, Niamh Murphy, Lois O’Connor, Joan O’Donnell, Piers Mook, Richard G Pebody, Nick Bundle
Journal: Eurosurveillance (2022)

Background Underlying conditions are risk factors for severe COVID-19 outcomes but evidence is limited about how risks differ with age. Aim We sought to estimate age-specific associations between underlying conditions and hospitalisation, death and in-hospital death among COVID-19 cases. Methods We analysed case-based COVID-19 data submitted to The European Surveillance System between 2 June and 13 December 2020 by nine European countries. Eleven underlying conditions among cases with only one condition and the number of underlying conditions among multimorbid cases were used as exposures. Adjusted odds ratios (aOR) were estimated using 39 different age-adjusted and age-interaction multivariable logistic regression models, with marginal means from the latter used to estimate probabilities of severe outcome for each condition–age group combination. Results Cancer, cardiac disorder, diabetes, immunodeficiency, kidney, liver and lung disease, neurological disorders and obesity were associated with elevated risk (aOR: 1.5–5.6) of hospitalisation and death, after controlling for age, sex, reporting period and country. As age increased, age-specific aOR were lower and predicted probabilities higher. However, for some conditions, predicted probabilities were at least as high in younger individuals with the condition as in older cases without it. In multimorbid patients, the aOR for severe disease increased with number of conditions for all outcomes and in all age groups. Conclusion While supporting age-based vaccine roll-out, our findings could inform a more nuanced, age- and condition-specific approach to vaccine prioritisation. This is relevant as countries consider vaccination of younger people, boosters and dosing intervals in response to vaccine escape variants.
Redox regulation of the immune response
Authors: Gerwyn Morris, Maria Gevezova, Victoria Sarafian, Michael Maes
Journal: Cellular and Molecular Immunology (2022)

Abstract The immune-inflammatory response is associated with increased nitro-oxidative stress. The aim of this mechanistic review is to examine: (a) the role of redox-sensitive transcription factors and enzymes, ROS/RNS production, and the activity of cellular antioxidants in the activation and performance of macrophages, dendritic cells, neutrophils, T-cells, B-cells, and natural killer cells; (b) the involvement of high-density lipoprotein (HDL), apolipoprotein A1 (ApoA1), paraoxonase-1 (PON1), and oxidized phospholipids in regulating the immune response; and (c) the detrimental effects of hypernitrosylation and chronic nitro-oxidative stress on the immune response. The redox changes during immune-inflammatory responses are orchestrated by the actions of nuclear factor-κB, HIF1α, the mechanistic target of rapamycin, the phosphatidylinositol 3-kinase/protein kinase B signaling pathway, mitogen-activated protein kinases, 5' AMP-activated protein kinase, and peroxisome proliferator-activated receptor. The performance and survival of individual immune cells is under redox control and depends on intracellular and extracellular levels of ROS/RNS. They are heavily influenced by cellular antioxidants including the glutathione and thioredoxin systems, nuclear factor erythroid 2-related factor 2, and the HDL/ApoA1/PON1 complex. Chronic nitro-oxidative stress and hypernitrosylation inhibit the activity of those antioxidant systems, the tricarboxylic acid cycle, mitochondrial functions, and the metabolism of immune cells. In conclusion, redox-associated mechanisms modulate metabolic reprogramming of immune cells, macrophage and T helper cell polarization, phagocytosis, production of pro- versus anti-inflammatory cytokines, immune training and tolerance, chemotaxis, pathogen sensing, antiviral and antibacterial effects, Toll-like receptor activity, and endotoxin tolerance.